Kim, Kyung-Tai Cho, Doo-Wan Cho, Jae-woo Im, Wan-Jung Kim, Da-Hee Park, Jong-Hyun Park, Ki Duk Yang, Young-Su Han, Su-Cheol 2024-01-19T08:32:46Z 2024-01-19T08:32:46Z 2023-07-13 2023-10 1976-8257 https://pubs.kist.re.kr/handle/201004/113243 A novel reversible monoamine oxidase B inhibitor, KDS2010, has been developed as a therapeutic candidate for neurodegenerative diseases. This study investigated its potential toxicity in non-human primates before human clinical trials. Daily KDS2010 doses (25, 50, or 100 mg/kg) were orally administered to cynomolgus monkeys (1 animal/sex/group, 4 males and 4 females) for 2 weeks to determine the dose range. One male was moribund, and one female was found dead in the 100 mg/kg/day group. One male was also found dead in the 50 mg/kg/day group. The death was considered an adverse effect in both sexes since distal tubules/collecting duct dilation and hypertrophy in the epithelium of the papillary duct were observed in their kidneys. Based on dose range finding results, KDS2010 (10, 20, or 40 mg/kg/day) was administered orally for 4 weeks, and animals were given 2 weeks for recovery. No significant changes were observed during daily clinical observations and macro-and microscopic examinations, including body weight, food consumption, hematology, clinical chemistry, and organ weight. And, the kidney was seen as the primary target organ of KDS2010 in the 2 weeks study, but no adverse effect was observed in the 4 weeks study. Therefore, 40 mg/kg/day is considered the no-observed-adverse-effect level in both sexes of cynomolgus monkeys. English 한국독성학회 Two weeks dose range-finding and four weeks repeated dose oral toxicity study of a novel reversible monoamine oxidase B inhibitor KDS2010 in cynomolgus monkeys Article 10.1007/s43188-023-00182-4 1 Toxicological Research, v.39, no.4, pp.693 - 709 Toxicological Research 39 4 693 709 N scie scopus kci ART003005835 001013073700001 2-s2.0-85162925432 Toxicology Toxicology Article PARKINSONS-DISEASE SAFINAMIDE Novel selective monoamine oxidase B inhibitor KDS2010 Non-human primate Acute oral toxicity test No-observed-adverse-effect level